Glucocorticoids trigger Alzheimer disease-like pathobiochemistry in rat neuronal cells expressing human tau
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Ημερομηνία
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Περιοδικό ISSN
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Είδος περιοδικού
peer reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
J Neurochem
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Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Amyloid precursor protein (APP) mis-processing and aberrant tau hyperphosphorylation are causally related to the pathogenesis and neurodegenerative processes that characterize Alzheimer's disease (AD). Abnormal APP metabolism leads to the generation of neurotoxic amyloid beta (Ab), whereas tau hyperphosphorylation culminates in cytoskeletal disturbances, neuronal dysfunction and death. Many AD patients hypersecrete glucocorticoids (GC) while neuronal structure, function and survival are adversely influenced by elevated GC levels. We report here that a rat neuronal cell line (PC12) engineered to express the human ortholog of the tau protein (PC12-htau) becomes more vulnerable to the toxic effects of either Ab or GC treatment. Importantly, APP metabolism in GC-treated PC12-htau cells is selectively shifted towards increased production of the pro-amyloidogenic peptide C99. Further, GC treatment results in hyperphosphorylation of human tau at AD-relevant sites, through the cyclin-dependent kinase 5 (E. C. 2.7.11.26) and GSK3 (E. C. 2.7.11.22) protein kinases. Pulse-chase experiments revealed that GC treatment increased the stability of tau protein rather than its de novo synthesis. GC treatment also induced accumulation of transiently expressed EGFP-tau in the neuronal perikarya. Together with previous evidence showing that Ab can activate cyclin-dependent kinase 5 and GSK3, these results uncover a potential mechanism through which GC may contribute to AD neuropathology.
Περιγραφή
Λέξεις-κλειδιά
alzheimer's disease, amyloid precursor protein, glucocorticoids, pc12 cells, rat neurons, tau, amyloid precursor protein, glycogen-synthase kinase-3-beta, transgenic mice, in-vivo, hyperphosphorylated-tau, induced neurotoxicity, hippocampal atrophy, oxi
Θεματική κατηγορία
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Σύνδεσμος
<Go to ISI>://000259949900008
http://onlinelibrary.wiley.com/store/10.1111/j.1471-4159.2008.05613.x/asset/j.1471-4159.2008.05613.x.pdf?v=1&t=h279w0a2&s=e19943671f4cc29aad88a942da42eb4f3f851e59
http://onlinelibrary.wiley.com/store/10.1111/j.1471-4159.2008.05613.x/asset/j.1471-4159.2008.05613.x.pdf?v=1&t=h279w0a2&s=e19943671f4cc29aad88a942da42eb4f3f851e59
Γλώσσα
en
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Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών